PXD055376 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Nucleus-Translocated GCLM Promotes Chemoresistance in Colorectal Cancer through a Moonlighting Function |
Description | Emerging evidence indicates that metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. In this study, utilizing a metabolic CRISPR-Cas9 knockout library screen, we observed that loss of Glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably heightens the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B-repressing factor (NKRF), a known inhibitor of NF-κB signaling, to promote NF-κB activity and subsequently facilitate chemoresistance. In response to platinum drug treatment, P38 MAPK phosphorylates GCLM at T17, resulting in its recognition by importin a5 and subsequent nuclear translocation. Furthermore, elevated expression of nuclear GCLM correlates with unfavorable prognosis and poor benefit from standard chemotherapy. Overall, our work shed light on the essential nonmetabolic role and posttranslational regulatory mechanism of GCLM in enhancing NF-κB activity and subsequent chemoresistance. |
HostingRepository | PRIDE |
AnnounceDate | 2024-11-15 |
AnnouncementXML | Submission_2024-11-14_21:55:18.456.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jinfei Lin |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-08-30 00:43:19 | ID requested | |
⏵ 1 | 2024-11-14 21:55:18 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Nuclear GCLM |
Moonlighting function |
NKRF |
Phosphorylation |
Chemoresistance;LC-MS/MS |
Contact List
Jin-fei Lin |
contact affiliation | Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China. |
contact email | linjf@sysucc.org.cn |
lab head | |
Jinfei Lin |
contact affiliation | Sun Yat-sen University Cancer Center |
contact email | linjf@sysucc.org.cn |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD055376
- Label: PRIDE project
- Name: Nucleus-Translocated GCLM Promotes Chemoresistance in Colorectal Cancer through a Moonlighting Function